Antimicrobial chemical compositions

ABSTRACT

Antimicrobial chemical compositions comprise an aluminum phosphate (AlP) solid dispersed within a binding polymer, wherein one or more bioactive materials are disposed within AlP forming a bioactive-AlP complex. The complex may comprise the bioactive material chemically bonded with the AlP, physically combined with the AlP, or a combination of both. The complex may be formed according to precipitation, condensation and sol-gel methods of forming. The complex is engineered to provide a controlled delivery of the bioactive material or a constituent thereof upon exposure to moisture to give a desired level of antimicrobial resistance to a film or composite formed from the composition of at least about 30 μg/m 2 , and may also provide a desired degree of corrosion resistance through the release of passivating phosphate anion. Such antimicrobial chemical compositions provide an improved degree of active, long-term resistance to a broad range of micro-organisms when compared to known antimicrobial chemical compositions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a continuation of and claims priority fromU.S. patent application Ser. No. 14/799,490, filed Jul. 14, 2015, nowU.S. Pat. No. 9,801,385, issued Oct. 31, 2017, which is a continuationof U.S. patent application Ser. No. 13/448,253, filed on Apr. 16, 2012,now U.S. Pat. No. 9,078,445, issued Jul. 14, 2015, which applicationsare herein incorporated by reference in their entirety.

FIELD OF THE INVENTION

This invention relates to chemical compositions having antimicrobialproperties and, more specifically, to chemical compositions that arespecially formulated to include an aluminum phosphate complex comprisingone or more antimicrobial agents, and methods for making the same.

BACKGROUND OF THE INVENTION

Chemical compositions formulated to include one or more antimicrobialagents to provide antimicrobial properties, e.g., provided in the formof a coating composition or the like for forming a film layer on anunderlying substrate surface, are known in the art. Such antimicrobialchemical compositions make use of antimicrobial agents known to providesome degree of protection against unwanted micro-organisms.

Conventional antimicrobial chemical compositions known in the art, e.g.,formulated products such as water-based paints and coatings, includebiocides incorporated therein to preserve the liquid composition duringstorage from spoilage by micro-organisms. Antimicrobial protection isafforded from such conventional paints and coatings by the incorporationof agents that prevent defacement of the applied, dry film in service bymold and/or mildew growth.

While conventional antimicrobial chemical compositions are known toprovide some protection against unwanted microorganisms, the protectionafforded is somewhat limited in both the degree of its activity, and thelength in time of its being able to offer a desired level of resistanceto unwanted microorganisms. This is largely due to the nature of theformulation and the limited activity of the antimicrobial agent disposedtherein, and the resulting inability to provide a highly-active andlong-lasting resistance to unwanted microorganisms. Thus, while suchconventional antimicrobial chemical compositions are capable ofproviding some degree of resistance to microorganisms, they are unableto provide a desired or needed level of microorganisms controlsufficient to meet the demands of certain end-use applications.

There is an unmet need to provide active, long-term resistance to abroad range of bacteria, mold, mildew, and other harmful micro-organismsto prevent collateral effects of illness and/or product spoilage due toinfection. Examples of target end-use applications where it is criticalto prevent infection and product spoilage from surface contact insensitive environments includes: hospitals and health care facilities;kitchens and food processing and storage areas; dairies; breweries;bathroom and rest room facilities; hotels; school, recreation,amusement, and sports facilities. While existing anti-microbialadditives may provide some degree of anti-microbial action, theireffectiveness in such formulated products as paints and coatings islimited by the amounts of material required to achieve anti-microbialaction, which exceeds: (1) cost constraints for the formulated product;(2) usage limitations relative to non-target toxicity; (3) the practicallimits for incorporation in the formulated product; and (4) which may belimited by the mechanism for delivery to the surface of the article tobe protected.

It is, therefore, desired that antimicrobial chemical compositions beformulated in a manner that provide a desired active, long-termresistance to a broad range of micro-organisms, including bacteria,mold, mildew, and other micro-biological species to prevent collateraleffects of illness and product spoilage, when compared to knownantimicrobial chemical compositions, thereby meeting the needs ofcertain end-use applications. It is desired that such antimicrobialchemical compositions be engineered in a manner facilitating the abilityto effectively customize, adjust and/or tailor changes in theperformance characteristics of the formulations for the purpose ofeffectively addressing the specific antimicrobial needs associated withdifferent end-use applications. It is further desired that suchantimicrobial chemical compositions be formulated from readily availablematerials, and/or be made by methods, that facilitate manufacturing thechemical compositions in a manner that does not require the use ofexotic equipment, that is not unduly labor intensive, and that iseconomically feasible.

SUMMARY OF THE INVENTION

Antimicrobial chemical compositions as described herein generallycomprise an aluminum phosphate (AlP) solid that is dispersed within abinding polymer. One or more bioactive materials are disposed within orcombined with the AlP to form a bioactive-AlP complex. A feature of thecomplex is that it is specifically engineered such that, when thecomposition is provided in the form of a dried film or composite, itprovides a controlled delivery of a bioactive constituent (derived fromthe bioactive material upon exposure to moisture) to the film orcomposite surface to provide a desired level of antimicrobialresistance. The AlP used to form the complex may be in amorphous form,in crystalline form, or in a combination thereof. In an exampleembodiment, the AlP comprises amorphous AlP.

The bioactive material or a bioactive constituent derived therefrom,used to form the complex may either be chemically bonded with, e.g.,provided in the backbone of, the AlP polymer, or may be physicallyincorporated, enmeshed, encapsulated, or intertwined with the AlPpolymer, depending on the particular method used to make the complex.The bioactive material can be organic and/or can be a metal salt oroxide such as those including silver salts, copper salts, zinc salts,calcium salts, and combinations thereof, and/or can be a metal ion suchas those including silver, copper, zinc, calcium, and combinationsthereof. Binding polymers used to form the composition can includepolyurethanes, polyesters, solvent-based epoxies, solventless epoxies,water-borne epoxies, epoxy copolymers, acrylics, acrylic copolymers,silicones, silicone copolymers, polysiloxanes, polysiloxane copolymers,alkyds and combinations thereof.

In an example embodiment, the AlP is engineered to provide a controlleddelivery of the bioactive constituent when the chemical composition isin a cured form, e.g., in the form of a coating film or a compositestructure, of from about 5 to 1,000 ppm, preferably about 10 to 900 ppm,and most preferably from about 15 to 800 ppm. In an example embodiment,it is desired to provide at controlled delivery of at least 100 ppm orgreater of the bioactive constituent. The amount of the bioactivematerial, e.g., Ag, in the complex may be in the range of from about 1to 10 percent by weight, preferably from about 2 to 8 percent by weight,and more preferably from about 3 to 6 percent by weight based on thetotal weight of the complex. The ratio of phosphate to aluminum in thecomplex is in the range of from about 0.5:1 to 1.5:1. The bioactive-AlPcomplex in the chemical composition comprises from about 0.1 to 2percent of the dry film weight, or 20 to 1,000 ppmw of bioactiveconstituent, e.g., Ag in the paint. In a preferred embodiment, aneffective leaching rate, that is, amount of bioactive constituent, e.g.,Ag, released on the surface of a cured coating or cured compositecomprising the bioactive-AlP complex is at least about 30 μg/m², and ispreferably about 36.9 μg/m² or >2 μg/L in a rinse for bioactivity.

In an example embodiment, the antimicrobial chemical composition mayalso provide a desired degree of corrosion resistance, e.g., whenformulated as a coating for use with metallic substrates. In suchembodiment, the AlP is formulated to provide, in addition to thecontrolled release/delivery of bioactive constituent, a controlleddelivery of passivating anion such as phosphate anion upon exposure tomoisture. In an example embodiment, such antimicrobial chemicalcomposition may provide a controlled delivery of phosphate anion ofgreater than about 100 ppm.

Antimicrobial chemical compositions as described herein are made byfirst forming the bioactive-AlP complex, which comprises forming an AlPby combining a desired aluminum source, with a desired phosphate sourceunder suitable reaction conditions, e.g., in an aqueous solution atsuitable pH and suitable temperature, to form the AlP. The bioactivematerial is added to the AlP during and/or after the step of forming theAlP so that the bioactive material is dispersed or combined with theAlP, thereby forming the bioactive-AlP complex. If desired, further AlPcan be added to the bioactive-AlP complex before combining the complexwith the binding polymer.

According to one example method of making, the bioactive material isadded to the AlP after it has been formed, in which case the resultingbioactive-AlP complex comprises the bioactive material physicallyincorporated, enmeshed, encapsulated, or intertwined with the AlPpolymer. According to another example method of making, the bioactivematerial is added to the AlP during formation of the AlP, in which casethe resulting bioactive-AlP complex is formed in-situ with the ALP andcomprises a bioactive constituent of the bioactive material chemicallybonded to the AlP polymer, e.g., as part of the ALP polymer backbone.

Antimicrobial chemical compositions as described herein are specificallyengineered to provide active, long-term resistance to a broad range ofmicro-organisms, including bacteria, mold, mildew, and othermicro-biological species to prevent collateral effects of illness andproduct spoilage, when compared to known antimicrobial chemicalcompositions, thereby meeting the needs of certain formulated end-useapplications, wherein such applications include paints, coatings,adhesives, composites, cements, plastics and the like. Theseantimicrobial chemical compositions are made from readily availablematerials and/or by methods that facilitate manufacturing in a manneravoiding exotic equipment, which is not unduly labor intensive, and thatis economically feasible.

DETAILED DESCRIPTION

Antimicrobial chemical compositions as described herein generallycomprise an aluminum phosphate (AlP) that is dispersed within a bindingpolymer that forms the bulk matrix of the composition. One or morebioactive materials are disposed within the aluminum phosphate, therebyforming a bioactive-AlP complex, and the and the aluminum phosphate isspecifically engineered to provide controlled delivery or release of abioactive constituent derived from the bioactive material upon exposureto moisture. Such antimicrobial chemical compositions are made by anumber of methods described herein, and can be formulated for use aspaints, coatings, adhesives, composites, cements, plastics, and thelike.

Aluminum phosphates useful in this regard include amorphous aluminumphosphates, crystalline aluminum phosphate, and combinations thereof.Example aluminum phosphates useful in this regard are amorphous aluminumphosphates (AAlPs), and preferred AAlPs are amorphous aluminumorthophosphates. While the use of AAlPs is desired because AAlPs havebeen shown to have certain characteristic properties, making them wellsuited for use as a carrier to the bioactive material, crystalline AlPsand combinations of amorphous and crystalline AlPs are also understoodto be useful in this regard and within the scope of the antimicrobialchemical compositions as disclosed herein.

In an example embodiment, the amorphous aluminum orthophosphates areamorphous aluminum hydroxy phosphates. Amorphous aluminum hydroxyphosphates provide uniform dispersion properties within the compositionand the dispersion remains stable throughout the shelf-life of theformulation. The hydroxyl content of the amorphous aluminum hydroxyphosphate provides matrix stability by providing hydrogen bonds withsuitable groups of the binding polymer of the formulation, e.g., such ascarboxyl groups, amino groups, hydroxyl groups, acid groups and thelike. This feature is unique to the amorphous aluminum hydroxyphosphate, and is not present in crystalline or other types of amorphousphosphates, and for this reason help to provide uniform dispersionproperties.

AlPs used to form antimicrobial chemical compositions disclosed hereinare specially designed to have a high level of compatibility with avariety of different binding polymers or binding polymer systems usefulfor formulating such end-use applications, thereby providing a highdegree of flexibility and choice in formulating such compositions tomeet the needs and conditions of a variety of end-use applications in anumber of different end-use industries.

Controlled delivery and/or release of the bioactive constituent withinthe chemical composition is largely dependent on the diffusion rate ofthe bioactive constituent through the bulk matrix of the composition,whether in the form of a coating or a composite. The diffusion rate ofthe bioactive constituent is dependent on the structural features of thebulk matrix that control bioactive constituent and water transport.These features include, but are not limited to, cross-link density,pigment to volume ratio (PVC), nature of the bioactive material carrier,hydrophilicity of components, and the polarity of the components.

Antimicrobial chemical compositions as disclosed herein use AlP as thebioactive carrier material, which AlP is engineered to provide acontrolled diffusion of both moisture to the bioactive materialcontained therein, and a diffusion or delivery or release of thebioactive constituent to the surface of a coating or compositecomprising such AlP, for purposes of providing a desired degree ofantimicrobial resistance. Accordingly, the bioactive material isincorporated into the AlP, which has been specifically made to moderateand control the solubility of the bioactive constituent, and to controlthe diffusion of the dissolved bioactive constituent through thecomposition film or composite bulk matrix.

A characteristic/parameter of the AlP discovered to have an influenceover the diffusion of moisture and delivery of the bioactive constituentis the porosity of the AlP molecule. A feature of AlP complexes asdisclosed herein is the ability to engineer the morphology and theporosity of such complexes by choice of synthesis method. As usedherein, the term “engineered porosity” is defined as the volume of spaceexisting within a solid material consisting of particle voids,interstitial space between particles in particle aggregates, andinterstitial space between aggregates in agglomerates. Mercuryporosimetry is used to characterize the porosity properties of solidsand pigments. Key measurements include:

-   1. Total intrusion volume (ml/g)—measures the overall space in the    sample into which mercury can be absorbed as a function of pressure.-   2. Total pore area (m²/g)—converts volume to area and defines how    much area is occupied by the total intrusion volume.-   3. Average pore diameter (4V/A=μm)—shows the distribution of volume    by area, i.e., how much volume on the average goes into different    pore sizes.-   4. BET (m²/g)—is the measure of total surface area accessible to    nitrogen gas under test conditions. BET and porosity correlate.

AlP complexes comprising a metal salt or metal ion, e.g., such assilver, as the bioactive material and formed by sol-gel method (asdescribed in better detail below) result in the formation of nano-sizedprimary particles incorporated into aggregates of very-high surface areaand porosity. An advantage of having such high surface area and porosityis that it ensures optimum diffusion contact with water and subsequentrelease of the silver ion in the film formed by the binding polymer bulkmatrix, thereby promoting uniform distribution of the complex throughoutthe film or composite, and promoting a relatively rapid release of thebioactive material from the complex upon contact with water.

AlP complexes comprising a metal salt or metal ion, e.g., such assilver, as the bioactive material and prepared by the sol-gel methodhave BET surface areas ranging from about 100 and 250 m²/g, andpreferably between about 125 and 200 m²/g, and most preferably betweenabout 140 and 160 m²/g. Such AlP complexes have a total intrusion volumeof between about 1 and 2 mL/g, and preferably between about 1.3 and 1.8mL/g. Such AlP complexes have an average pore diameter of from about0.02 to 0.06 μm, and preferably between about 0.04 and 0.05 μm.

In contrast, AlP complexes comprising a metal salt or metal ion, e.g.,such as silver, as the bioactive material and formed by precipitation orcondensation method (as described in better detail below) result in theformation of nano-sized primary particles incorporated into aggregatesof relatively low surface area and low porosity. An advantage of havinglow surface area and porosity is that it ensures reduced degree ofdiffusion contact with water and subsequent release of the silver ion inthe film or composite formed by the binding polymer bulk matrix, therebypromoting uniform distribution of the complex throughout the film orcomposite, and promoting a relatively slow release of the bioactivematerial from the AlP complex upon contact with water.

AlP complexes comprising a metal salt or metal ion, e.g., such assilver, as the bioactive material and prepared by precipitation orcondensation method have BET surface areas ranging from about 2 to 10m²/g, total intrusion volumes ranging from about 0.5 to 0.9 mL/g, andhave average pore diameters ranging from about 0.4 to 0.6 μm.

Thus, a feature of AlPs useful for making antimicrobial chemicalcompositions is that they have an engineered porosity calculated toprovide the desired rates of moisture diffusion and delivery ofbioactive constituent that promotes a desired degree of activity andantimicrobial resistance when placed in an end-use application.

Thus, the desired porosity of the AlP is understood to vary depending onthe certain requirements called for by each different end-useapplication. However, it is generally desired that the porosity of theAlP be not so great so as to rapidly extinguish the bioactiveconstituent upon exposure to moisture, e.g., be highly active butprovide a greatly reduced effective service life. The loading of thebioactive material and/or the type of bioactive material that is usedwill also influence the activity and effective service life.Accordingly, the porosity of the AlP reflects a balance or compromisebetween a desired degree of antimicrobial activity and a desiredeffective service life for a given amount or general loading range of agiven bioactive material.

The porosity of the AlP is engineered during the process of making theAlP and/or during post formation processing, e.g., drying and/or otherheat treatment, as described in greater detail below.

AlPs as disclosed herein, in addition to serving as the bioactivematerial carrier to provide desired controlled delivery/release of thebioactive constituent, provide anticorrosion protection through thedelivery of phosphate anion when exposed to moisture. Accordingly, forthose end-use applications calling for both antimicrobial andanticorrosion properties, e.g., in the case where the composition isformulated for use as a coating on a metal substrate, the AlP can alsobe engineered to provide a controlled delivery of the phosphate anion toprovide a desired degree of corrosion protection through passivation toa metal substrate.

In an example embodiment, wherein such corrosion resistance is alsodesired, the AlP is engineered to release in the range of from about 50to 500 ppm, and preferably 100 to 200 ppm of the passivating phosphateanion when present in a cured film or composite placed into an end-useapplication. The amount of passivating anion to be delivered depends ona number of different factors such as the loading or amount of the AlPused, the type of binding polymer that is used, the type of metallicsubstrate being protected, and the type of environment present in theend-use application. In a preferred embodiment, where the metallicsubstrate being protected comprises iron and the corrosion environmentcomprises water, oxygen, and other corrosive salts, the AlP isengineered to release approximately 160 ppm of the passivating phosphateanion.

Example binding polymers include those currently used for making knownantimicrobial chemical compositions, and can be selected from thegeneral group including water-borne polymers, solvent-borne polymers,hybrids and combinations thereof. Example water-borne polymers usefulfor making anticorrosion coating compositions include acrylic andacrylic copolymers, alkyd, epoxy, polyurethane, and silicone, andpolysiloxane polymers. Example solvent-borne and/or non-aqueous polymersuseful for making anticorrosion coating compositions include acrylic andacrylic copolymers, epoxy, polyurethane, silicone, polysiloxane,polyester, and alkyd. Preferred binding polymers include acryliccopolymer latex, alkyd, polyurethane and epoxy polymers.

In an example embodiment, antimicrobial chemical compositions comprisein the range of from about 15 to 75 weight percent, preferably in therange of from about 20 to 60 weight percent, and more preferably in therange of from about 20 to 35 weight percent of the binding polymer basedon the total weight of the chemical composition when in a pre-cured orwet state. An antimicrobial chemical composition comprising less thanabout 15 percent by weight of the binding polymer may include a greateramount of the bioactive material (present as the bioactive-AlP complex)than necessary to provide a desired degree of antimicrobial protection.An antimicrobial chemical composition comprising greater that about 75percent by weight of the binding polymer may include an amount of thebioactive material (present as the bioactive-AlP complex) that isinsufficient to provide a desired degree of antimicrobial resistance.While certain amounts of the binding polymer have been provided, it isto be understood that the exact amount of the binding polymer that isused to formulate antimicrobial chemical compositions will varydepending on such factors as the type of binding polymer used, the typesand amounts of other materials used to form the chemical composition,the type and/or quantity of bioactive material that is used, and/or theparticular end-use antimicrobial application.

Bioactive materials or agents useful in forming antimicrobial chemicalcompositions described herein can be selected from a variety ofbioactive materials and/or species including, but not limited to: (1)antimicrobial additives comprising organic molecules that are eitherbiocidal (kill microbes) or biostatic (inactivate microbes); (2)bio-pesticides, typically peptides that have biostatic or biocidaleffects on microbes; (3) natural products that inhibit or prevent thegrowth of the target organisms naturally; (4) “friendly” bacteria thatinterfere with the growth and/or development of target microbes; (5)minerals and metals that release or produce antimicrobial species inresponse to certain environmental conditions, and (6) combinationsthereof. Organic antimicrobial additives and metal-based biocides havemost commonly been used to impart antimicrobial properties to formulatedproducts.

Metal-based materials useful as bioactive materials or agents includemetal ions and metal salts. Suitable metal ions include those selectedfrom the group consisting of silver, copper, zinc, calcium, andcombinations thereof. Suitable metal salts include salts of theabove-identified metal ions. In an example embodiment, silver is adesired bioactive material because it has several advantages, providedthat it can be made compatible with the formulation of the bindingpolymer in which is it incorporated, and provided that the silver can bemaintained in an active state within the formulation for delivery to thesurface upon exposure to moisture in a consistent and cost effectivemanner. Silver is advantageous over organic materials because it hashigher degree of thermal stability, a lower level of toxicity tonon-target organisms than typical organic biocides, and has a higherlevel of UV stability.

Silver ion (Ag⁺) is bioactive, and in sufficient concentration kills avariety of microorganisms. Silver has proven anti-microbial activity andis known to be effective against certain antibiotic-resistant bacteria.It has broad spectrum anti-microbial activity and minimal toxicitytoward mammalian cells. Silver is typically formulated or incorporatedas an active ingredient in a carrier component (at concentration levelstypically <5% by weight) such as glass, silica, or zeolite. Themechanism of action by which silver-based materials controlmicro-organisms involves the release of silver ion in response toambient moisture. The silver ion is formed by contact with water, andthe ion contacts the organism and interacts with multiple binding sitesin the organism. As the silver ion is transferred into the cells of thetarget organism metabolic, the respiratory functions of the cell arealtered and eventually cease, causing the cell to die.

Suitable sources of silver for use as the bioactive material includesilver salts such a silver nitrate and silver chloride, wherein silvernitrate (AgNO₃) is preferred. Silver nitrate is extremely soluble (122grams per 100 milliliters of water at 0° C.) and this solubilitypresents a special challenge for controlled delivery of the bioactivematerial from a formulated product, such as an antimicrobial coating orcomposite. Silver nitrate is useful as a bioactive material as long asthe delivery of silver ion from the formulated coating or composite tothe surface is controlled at a rate and in a concentration balanced tosupply the minimum control level for the target service life. Too rapidof a delivery will result in excessive concentration of silver ion onthe surface to be protected, causing a discoloration of the surfaceand/or a rapid depletion the available reserves of silver nitrate in thebulk matrix, thereby reducing effective service life.

As discussed above, the AlP is made having an engineered porosity toprovide a controlled diffusion rate and release/delivery of thebioactive constituent, e.g., silver ion, through the bulk matrix of thecoating or composite. The incorporation of silver nitrate directly intoa coating as a free component will not allow for controlled release. Itis necessary to incorporate the silver nitrate (or silver ion source) inthe AlP as engineered to moderate and control the solubility of thesilver salt, control the diffusion of the dissolved silver ion throughthe film or composite matrix, and to control the resulting delivery ofthe silver ion to the surface.

As noted above, the porosity properties of AlP are engineered to providea mechanism to control such reactions as hydrolysis and dissolution.Additionally, the AlP can be made hydroscopic so that it attracts waterto itself specifically in a bulk matrix, thereby providing a medium fordissolution interactions. The feature of engineered porosity is thebasis for controlled dissolution and ion release. In the case of silverion, the diffusion rate of silver ion is dependent on the surface areaand the porosity of the AlP. This also moderates the overall transportrate of the silver ion through the bulk matrix. Specifically, when watercontacts the bulk matrix it is absorbed, and when the water in the bulkmatrix contacts the highly soluble silver disposed within thebioactive-AlP complex (either as silver nitrate physically encapsulatedwithin the AlP or as a silver ion chemically bonded to the AlP) thesilver species is dissolved and the silver ion undergoes diffusionthrough the bulk matrix to the surface.

A feature of antimicrobial compositions as disclosed herein is that suchcompositions comprise the use of the AlP complex disposed within thebulk matrix of the binder polymer, wherein the AlP complex has a rate ofbioactive constituent delivery that can be the same or different thanthe rate of bioactive constituent (released from the complex) migrationor diffusion through the binder polymer. Thus, a formulator can engineerthe porosity of the AlP complex to provide a desired release rate of thebioactive constituent therefrom, and can further engineer theformulation (by use of different binding polymers, fillers and the like)to influence the migration or diffusion rate of the bioactiveconstituent through the composition to meet certain end-use applicationdemands. The combination of these features, i.e., the release rate ofthe bioactive constituent from the AlP complex, and the migration ordiffusion rate of such released bioactive constituent through the binderpolymer bulk matrix, provide for an enhanced level of antimicrobialcomposition customization not otherwise available. Such customization ofrelease rates and migration/diffusion rates operate to provide a vastrange of antimicrobial compositions that can be specifically tailored toaddress a variety of end-use applications.

The amount or concentration of the bioactive material that isincorporated into the AlP can and will vary depending on such factors asthe type of bioactive material used, the nature of the binding polymerused to form the coating or composite matrix, the type of AlP(amorphous, crystalline, or a combination thereof), and the engineeredporosity of the AlP. Thus, the properties of the bioactive-AlP complex,such as the bioactive material concentration and the AlP engineeredporosity can be controlled to address various exposure conditions suchas temperature, relative humidity, ultra-violet exposure and the like.

In an example embodiment, it is desired that a sufficient amount of thebioactive material be present, and that the AlP have an engineeredporosity that will result in the composition, when provided in the formof a dried film or composite, to provide a controlled delivery of thebioactive constituent (derived from contacting the bioactive materialwith moisture) of from about 5 to 1,000 ppm, preferably of from about 10to 900 ppm, and more preferably in the range of from about 15 to 800ppm. In a particular embodiment, where the bioactive constituent issilver ion, a desired optimum controlled delivery of the silver ion isgreater than about 100 ppm, and most preferably about 120 ppm. In apreferred embodiment, an effective leaching rate, that is, amount ofbioactive constituent, e.g., Ag, released on the surface of a curedcoating or cured composite comprising the bioactive-AlP complex is atleast about 30 μg/m², and is preferably about 36.9 μg/m² or >2 μg/L in arinse for bioactivity.

In order to provide the desired controlled delivery of the bioactiveconstituent, it is desired that certain amount of the bioactive materialbe used when forming the bioactive-AlP complex. In an exampleembodiment, the AlP complex comprises from about 1 to 10 percent byweight of the bioactive material, preferably from about 2 to 8 percentby weight of the bioactive material, and more preferably from about 3 to6 percent by weight of the bioactive material based on the total weightof the bioactive-AlP complex.

Additionally, it has been discovered that mixed anti-microbial complexesbased on silver and other bio-active materials can be synthesized whichhave synergistic effects. For example, in addition to silver-ALPcomplexes, other bio-active metals as copper and/or zinc can beintroduced into the complex by their inclusion in the synthesis processas better described below. Further, certain organic bio-active moleculescan be introduced into the complex through physicaladsorption/encapsulation or by actual reaction/condensation with thephosphate group of the complex. This provides a controlled releasemechanism through subsequent hydrolysis in the bulk film by thediffusion of water.

AlPs can be made through the selective combination the materials notedabove. The following selected methods of preparation are provided belowas examples, and it is to be understood that other methods ofpreparation other than those specifically disclosed may be used. Whilethe methods disclosed herein for making AlPs may reference and disclosethe formation of amorphous aluminum phosphate (AAlP), it is to beunderstood that such methods may also produce or be adapted to produceother forms of AlP, such as the various crystalline aluminum phosphateforms and/or mixtures of amorphous and crystalline aluminum phosphates,depending on the end-use antimicrobial application performanceproperties. Example crystalline forms of AlPs formed as disclosed hereininclude and are not limited to orthorhombic and triclinic aluminumorthophosphates. Accordingly, the methods disclosed herein areunderstood to be useful for making different forms of AP, depending onthe particular end-use applications and performance properties.

Binary Condensation Methods of Making

Generally, the AlP is an aluminum phosphate complex that is prepared bycombining a suitable aluminum salt, such as aluminum hydroxide, aluminumsulfate and the like with phosphoric acid or other phosphorus-containingcompound or material, depending on the particular type of aluminum saltselected for forming the aluminum phosphate. In an example embodiment, apreferred aluminum salt is aluminum hydroxide (Al(OH)₃), and a preferredsource of the phosphorus-containing ingredient is phosphoric acid(H₃PO₄). Example methods as disclosed herein comprise forming AlP by acondensation process, wherein the AlP is formed by the condensationreaction of the aluminum salt ingredient with the phosphorous-containingingredient to produce AlP particles in slurry form. The composition ofthe condensed solid resulting from such process of making depends on theratio of the aluminum metal to phosphate anion. The properties of theresulting complex, i.e., the AlP, depends on the processing parametersemployed during the condensation reaction, including choice of aluminumsalt, temperature, the physical state of the reactants, order ofaddition of reactants, rate of addition of reactants, the degree andduration of agitation, pretreatment of one or more of the reactants, andpost treatment of the resulting condensation product.

Generally speaking, the condensed solid that results from this method ofmaking, even after milling, has a very low oil absorption property andlow surface area (as measured by BET method) when compared to aluminumphosphate prepared by other known methods. Oil absorption is defined asthe amount (grams or pounds) of linseed oil required to wet out and fillthe voids spaces around a pigment, ASTM-D-281-84, which is a measure ofthe binder demand or the amount of binder resin that a pigment mayabsorb in a given formulation. High binder demand adds to formulationcost and can affect certain barrier properties of the dry film. This isfurther surprising because the aluminum phosphate made by the binarycondensation process disclosed herein also displays the controlledrelease property and water adsorption property usually associated withhigh surface area particles.

In an example embodiment, the condensed aluminum phosphate preparedherein has an oil absorption of less than about 50, preferably in therange of between about 10 to 40, and more preferably in the range ofbetween about 20 to 30. In contrast, AlP that is made by other methodshas an oil absorption of greater than about 50, and typically in therange of about 50 to 110.

In an example embodiment, the AlP prepared herein has a surface area ofless than about 20 m²/g, and preferably less than about 10 m²/g. In anexample embodiment, the surface area is in the range of between about 2to 8 m²/g, and more preferably in the range of between about 3 to 5m²/g. In contrast, AlP made by other methods has a surface area greaterthan 20 m²/g, e.g., from about 30 to 135 m²/g.

AlPs made as a binary condensation product can be produced according toleast five different methods, wherein two of which involve adding a basereactant to an acid reactant, one of which involves adding an acidreactant to a base reactant, one of which involves base-to-acid in-situaggregation, and one of which involves acid-to-base in-situ aggregation.In such methods, selected starting materials including an aluminumsource and a phosphorous source are combined under specific conditionsof controlled material delivery, temperature, and agitation. Thejudicious selection of starting materials and processing conditionsproduces AlPs having a material content and chemical structureintentionally created with the purpose of producing the above-notedengineered characteristics to provide the desired controlleddelivery/release of the bioactive constituent when formulated into acoating composition or composite.

As noted above, aluminum sources useful for forming AlP by binarycondensation method include aluminum salts, such as aluminum hydroxide,aluminum chloride, aluminum nitrate, aluminum sulfate, and the like.Preferred aluminum sources include aluminum hydroxide and aluminumsulfate. Phosphorous sources useful for forming AlP by condensationinclude phosphoric acid, and salts of phosphorus as orthophosphates oras polyphosphates. A suitable source of phosphorus is fertilizer gradephosphoric acid, from any origin, that has been clarified anddiscolored. For example, a commercial phosphoric acid containingapproximately 54% of P₂O₅ may be chemically treated and/or diluted withtreated water resulting in a concentration of approximately 20% of P₂.

AlPs useful for forming antimicrobial chemical compositions describedherein can be made according to a number of different methods, whichincludes at least five variations of the binary condensation process.The following selected methods of preparation are provided below asexamples, and it is to be understood that other methods of preparationother than those specifically disclosed may be used.

Example No. 1 Binary Condensation Formation of the AlP (Base-to-AcidRoute)

In an example embodiment, AlP is prepared by adding aluminum hydroxide(Al(OH)₃) to phosphoric acid (H₃PO₄). The H₃PO₄ was diluted with waterbefore being combined with the Al(OH)₃ and, prior to addition, theAl(OH)₃ was not wetted with water, although wetted Al(OH)₃ can be used.The reactants were quickly combined at room temperature without heatingto produce a white slurry. However, if desired, the reaction can beheated. The H₃PO₄ was 85 wt % in water provided by Sigma-Aldrich, andthe Al(OH)₃ was reagent grade provided by Sigma-Aldrich. Specifically,approximately 57.3 g (0.5 mole) H₃PO₄ was diluted with 50 g of waterbefore being combined with Al(OH)₃. Approximately 39 g (0.5 mole) ofAl(OH)₃ was added to the solution quickly and the mixture was stirredslowly at room temperature to wet the powder. An AlP condensed solid wasformed and existed as a dispersion of solid AlP particles in water. Inthis particular embodiment, the AlP particles existed primarily in theform of amorphous aluminum phosphate (AAlP). Diluting the H₃PO₄ prior toaddition of the Al(OH)₃ thereto is believed to contribute to formingexclusively AAlP, e.g., wherein there is little to no crystalline formproduced. The suspension was filtered to isolate the AlP particles. Theparticles were washed and dried to an appropriate temperature, which maybe less than about 300° C., and preferably from about 100° C. to 200° C.A feature of the AlP so formed is that it may be combined with a bindingpolymer, e.g., used for formulating an antimicrobial coatingcomposition, without the need for further heat treatment, tempering, orcalcining. While heating the AlP at the extreme temperatures noted abovemay be useful for driving off water, such may also initiate conversionof the AlP from an amorphous form to a crystalline form. It may bedesired to subject the AlP to elevated temperatures above 200° C., e.g.,of between 300° C. to 800° C., to either remove unwanted constituentstherefrom and/or to influence physical characteristics of the AlP thatmay influence its end-use performance properties or characteristics inthe antimicrobial composition. If a crystalline form of AlP is desired,the AlP so formed can be further heat treated or calcined to produce thedesired crystalline AlP.

Alternatively, the AlP was prepared by adding the Al(OH)₃ to the H₃PO₄.However, unlike the example embodiment disclosed above, the H₃PO₄ wasnot diluted before combining with the Al(OH)₃. However, beforecombining, the H₃PO₄ was heated. Additionally, prior to combining withthe H₃PO₄, the Al(OH)₃ was wetted with water. A feature of this methodof preparing is that it does not include the addition of free waterafter combination of the reactants, although it is to be understood thatthe AlP can be made according to this method by including the additionof free water. In an example embodiment, the H₃PO₄ was 85 wt % in waterprovided by Sigma-Aldrich, and the Al(OH)₃ was reagent grade provided bySigma-Aldrich. Specifically, approximately 57.6 g H₃PO₄ was heated to atemperature of about 80° C. Approximately 39 g of Al(OH)₃ was wettedwith about 2 g water and the wetted Al(OH)₃ was quickly added to theH₃PO₄ under fast mechanical stirring. An AALP solid was formed andexisted as a dough-like ball that was removed and stored at roomtemperature. A feature of the AlP so formed is that further treatment inthe form of filtering and washing was not necessary to isolate andobtain the desired AlP. Like the example embodiment disclosed above,such AlP was dried and formed into the desired particle size useful forforming the antimicrobial chemical composition.

Example No. 2 Binary Condensation Formation of the AlP (Base-to-AcidRoute)

In an example embodiment, AlP having the above-noted engineered physicalproperties or characteristics, e.g., porosity, is prepared by addingaluminum hydroxide (Al(OH)₃) to phosphoric acid (H₃PO₄) at an elevatedtemperature, e.g., at about 60° C., to form the desired AlP. The H₃PO₄was diluted with water before being combined with the Al(OH)₃ and, priorto addition, the Al(OH)₃ was combined with water to form a slurrycomprising between about 10 to 25 percent by weight, and in some casesup to about 40 percent by weight Al(OH)₃, depending on the grade of theAl(OH)₃. In preparing the Al(OH)₃ slurry, the water may be heated tofacilitate dispersion of the aluminum hydroxide powder, e.g., toovercome certain properties of a specific grade of aluminum hydroxide.The heated slurry may be maintained at an elevated temperature and addedto the acid. With very high-grade aluminum hydroxide, having a highdegree of purity and small particle size and distribution, the Al(OH)₃slurry can be made by adding to room temperature water.

The Al(OH)₃ slurry was added slowly to the diluted H₃PO₄ for the purposeof controlling the kinetics of the condensation reaction. In an exampleembodiment, the Al(OH)₃ slurry was added in a controlled manner, e.g.,in a drop-wise fashion or the like, to the H₃PO₄ over a period ofapproximately 10 minutes to about one hour. The combined reactants wereheated to a temperature of approximately 95° C., and the reactants weremixed together for a sufficient period of time, typically about 3 hours.In an example embodiment, the reaction takes place in a constant volumesystem that is essentially closed, e.g., a reflux condenser may beattached to maintain constant solvent volume (water) in the reactionsystem. In an example embodiment, the H₃PO₄ was 85 wt % in waterprovided by Sigma-Aldrich, and the Al(OH)₃ was reagent grade, providedby Sigma-Aldrich. Specifically, approximately 864 g of 85% dilute H₃PO₄was used, and the slurry was formed by combining 585 g of Al(OH)₃ with1,650 g of deionized water. The combined reactants were contained in amixing vessel and mixed at 1,300 to 1,500 rpms. Further water was addedto the reactants and the combination was mixed for approximately 30minutes to about 3 hours, e.g., more typically the latter.

If desired, a suitable chemical agent can be added to the reactants forthe purpose of reducing the solubility of the components of the motherliquor, thereby providing still further increased control over theoutcome of the reaction. In an example embodiment, such chemical agentcan be calcium hydroxide (Ca(OH)₂), soluble amines such asdiethylenetriamine (DETA), or the like.

An AlP condensed solid was formed and existed as a dispersion of solidacidic AlP particles in water. The suspension was filtered to isolatethe acidic AlP particles. The particles were washed with water one ormore times, and then filtered again. In an example embodiment, after theinitial filtering, the particles were washed with a volume of waterapproximately six times the volume of the precipitate before beingrefiltered. Successive washings operate to remove unreacted startingmaterial and any soluble byproducts from production. After beingrefiltered, the acidic AlP particles were reslurried by the addition ofwater, and were further treated in accordance with one of the followingthree different techniques.

In a first technique, the slurry is filtered to isolate the acidic AlPparticles and the particles are heated. In an example embodiment, theAlP particles are heated to a temperature of about 110° C. for about 24hours to drive off the water, and produce acidic AlP particles.Alternatively, the AlP particles are heated to a temperature of about250° C. for about 12 to 48 hours, and produce acidic AlP particles thatare both free of water and any by-products that decompose below 250° C.In addition, heat treatment at either temperature, but especially at theelevated temperature, provides the driving force to complete theconversion of any intermediates that may remain in the complex.

In a second technique, the slurry containing the acidic AlP isneutralized by adding a suitable neutralizing agent thereto. In anexample embodiment, the neutralizing agent is ammonium hydroxide (NH₄OH)that is added to the slurry in a sufficient amount to increase the pHand to neutralize the AP to a desired pH, typically 5.5 to 7.0. Theresulting slurry is filtered and the isolated AP particles are heated.In one example embodiment, the AlP particles are heated to a temperatureof about 110° C. for about 24 hours to drive off the water, and produceAlP particles. Alternatively, the AlP particles are heated to atemperature of about 250° C. for about 24 hours to both drive off waterand other unwanted chemical constituents, to produce AlP particles andto effect any final conversion or neutralization of surface adsorbed orbulk absorbed reactive species such as phosphate anion or hydrogenphosphate anion. Any reactive amine may be used for this conversion orneutralization step, including but not limited to diethylenetriamine,triethylenetetramine, 2-amino-2-methyl-1-propanol.

In a third technique, the slurry containing the acidic AlP isneutralized by adding a suitable neutralizing agent thereto. In anexample embodiment, the neutralizing agent is calcium hydroxide(Ca(OH)₂) that is added to the slurry in a sufficient amount to increasethe pH and neutralize the acidic AlP. The resulting slurry is filteredand the isolated AlP particles are heated. In one example embodiment,the AlP particles are heated to a temperature of about 110° C. for about24 hours to drive off the water, and produce AlP particles.Alternatively, the AlP particles are heated to a temperature of about250° C. for about 24 hours to both drive off water and other unwantedchemical constituents, and produce AlP particles. Other hydroxidecompounds of such divalent cations as barium, and magnesium may be usedin place of calcium to effect the neutralization or pH adjustment.

As described above in Example 1, the AlP produced according to themethods disclosed in Example 2 comprised AAlP. However, it is to beunderstood that crystalline AlP and/or combinations of AAlP andcrystalline AlP can be produced according to the methods disclosed,e.g., by running the condensation reaction at temperatures for periodsof time of less than 3 hours above 90° C. Maintaining the reactiontemperature between about 45 and 90° C., and preferably between about 60and 70° C. will produce AlP that is a combination of crystalline andamorphous forms. Running the reaction at a temperature below about 45°C. will produce primarily AlP in the amorphous form.

Example No. 3 Binary Condensation Formation of the AlP (Acid-to-BaseRoute)

It has been discovered that changing the order of addition changes thenature of the catalysis of the condensation reaction, i.e., adding theacid to the basic slurry results in slower localized pH change and thereaction is primarily base catalyzed. The AlP particles form slower andare smaller in localized areas in solution. The particles that form tendto have higher surface areas than particles formed by acid catalysis,and are less aggregated and agglomerated. In an example embodiment, theorder of addition in Example 2 is reversed, that is, the required amountof phosphoric acid is added slowly to the aluminum hydroxide slurry. Theslurry is prepared as described in Example 2. Phosphoric acid is addedslowly to the slurry over a period of approximately 30 minutes to onehour, and the resulting mixture is mechanically stirred and heated toabout 95° C. for at least 3 hours. The AlP particles are isolated andpurified, and dried as described in Example 2.

In addition to the acid-to-base route disclosed immediately above, ithas been discovered that such acid-to-base route can be further enhancedby first dissolving a certain amount of the aluminum hydroxide in thephosphoric acid before adding the acid solution to the slurry. In anexample embodiment, an amount of aluminum hydroxide, e.g., up to thesolubility limit of aluminum hydroxide, is dissolved separately in thephosphoric acid. In an example embodiment, AlP is prepared according toa two-step process. In a first step, a portion of the aluminumhydroxide, typically one third of the stoichiometric amount, is firstdissolved in phosphoric acid to form an acidic AlP solution. This acidicAlP solution contains all the phosphoric acid and phosphate needed tosatisfy the stoichiometry of the reaction for a product having thedesired 1:1 P to Al ratio. In a second step, the acidic AlP solution isthen added to a slurry containing the remaining amount of aluminumhydroxide required for stoichiometry. The combination undergoes reactionat ambient temperature to form an AlP condensed solid comprising adispersion of solid acidic AlP particles in water. Alternatively, thereaction can occur at elevated temperature conditions, e.g., of about95° C., which is preferred for reaction efficiency and kinetic controlof product forms. An advantage of this two-step approach is that part ofthe aluminum hydroxide required for the reaction is dissolved andpre-reacted before the acid solution is added to the slurry, therebyproviding a subsequent heterogeneous reaction that is less viscous andrequires less agitation, to thereby ensure more complete condensation.

Like the method disclosed in Example 2 above, such acid-to-base reactionroutes are ones that are preferably conducted under constant volumeconditions. The suspension was filtered to isolate the acidic AlPparticles. The particles were washed with water one or more times, andthen filtered again. In an example embodiment, after the initialfiltering, the particles were washed with a volume of waterapproximately six times the volume of the precipitate before beingrefiltered. In a preferred embodiment, the sequence is to filter andwash, which can be repeated any number of times to achieve the desireddegree of purity. The resulting rewashed AlP particles can then befiltered and dried at a temperature of approximately 110° C. for about24 hours to provide acidic AlP particles.

Alternatively, after rewashing, the AlP particles can be reslurried andthen neutralized by adding a suitable neutralizing agent, e.g., such asthose described above, thereto. In an example embodiment, a sufficientquantity of ammonium hydroxide (NH₄OH) was added to the reslurried AP,and the resulting mixture was filtered to isolate the AlP particles, andthe particles are heated. In an example embodiment, the AlP particlesare heated to a temperature of about 110° C. for about 24 hours to driveoff the water, and produce solid AAlP particles. Additionally, asdescribed above, it is to be understood that the method disclosed hereincan also be used to produce crystalline AlP or combinations of AAlP andcrystalline AlP, e.g., by running the reaction at temperatures in excessof about 90° C.

Example 4 Binary Condensation Formation of the AlP (Base-to-Acid In-SituAggregation)

In an example embodiment, AlP is prepared by adding aluminum hydroxide(Al(OH)₃) to phosphoric acid (H₃PO₄) to form the desired AlP, e.g., inthe manner disclosed above in Examples 1 and 2. However, unlike Examples1 and 2, the reaction is allowed to occur in an open system, wherein thereaction system is left open so as to allow solvent water tocontinuously evaporate, thereby causing the concentration of thereaction system to increase and its pH to decrease over time. Atperiodic intervals during the condensation reaction process, the waterlevel is replenished to the initial volume. The reaction slurry is thendiluted with an additional 50 g of water and stirred for 30 minutes tofurther facilitate dispersion of the AlP particles in the reactionslurry. The slurry is then filtered, washed with a volume of waterapproximately six times the volume of the precipitate, and filteredagain. This filter-wash-filter cycle can be repeated until the desiredpurity level is achieved. Usually one to three cycles is sufficient toremove unreacted starting material and unwanted reaction by-products.

It has been discovered that by allowing the volume to vary as described,the resulting change in system concentration and pH causes sequentialprecipitation of AlP “oligomers” in solution onto AlP particles alreadyformed and agglomerated. This sequential precipitation of AlP oligomersonto already-formed and agglomerated AlP particles operates to seal thesurface porosity of the pre-existing AlP aggregates and particles, e.g.,causing in-situ particle layering, which thereby reduces the surfaceporosity of such AlP aggregate and reduces such related properties asoil absorption. In an example embodiment, the AlP oligomers are AAlP andthe AlP particles already formed are AAlP.

As noted above, allowing water levels to cycle during the condensationcauses a change in the pH proportional to the concentration of theAl(OH)₃. When the volume decreases, the pH increases due to the higherconcentration of the Al(OH)₃, and the solubility decreases allowing AlPoligomers to agglomerate. Adding Ca(OH)₂ to the condensation medium mayalso effect a similar change in pH, causing the precipitation of AlP andsubsequent coating of pre-existing AlP particles. This process wouldalso incorporate the alkaline earth metal cations as counter-ions forresidual acid phosphate groups either adsorbed on the AlP particlesurface or bonded as a pendant component.

A condensed solid was formed and existed as a dispersion of solidacidic-coated AAlP particles in water. The suspension was filtered toisolate the acidic coated AlP particles. The particles were washed withwater one or more times, and then filtered again. In an exampleembodiment, after the initial filtering the particles were washed with avolume of water approximately six times the volume of the precipitatebefore being refiltered. Successive washings remove unreacted startingmaterial and any byproducts from production. After being refiltered, theacidic-coated AlP particles were reslurried by the addition of water,and were further heat treated. In an example embodiment, the slurry isfiltered to isolate the acidic coated AlP particles and the particlesare heated to a temperature of about 110° C. for about 24 hours to driveoff the water, and produce acidic coated AlP particles. Alternatively,the coated AlP particles are heated to a temperature of about 250° C.for about 12 to 48 hours, to produce dry acidic coated AP particles thatare both free of water and any by-products that decompose below 250° C.Additionally, as described above, it is to be understood that the methoddisclosed herein can be used to produce crystalline AlP, or acombination of AAlP and crystalline AlP.

Example 5 Binary Condensation Formation of AlP (Acid-to-Base In-SituAggregation)

In an example embodiment, AlP is prepared by adding phosphoric acid(H₃PO₄) to aluminum hydroxide (Al(OH)₃) to form the desired AlP, e.g.,in the manner disclosed above in Example 3. However, unlike Example 3,the reaction is allowed to occur in an open system, wherein the reactionsystem is left open so as to allow solvent water to continuouslyevaporate, thereby causing the concentration of the reaction system toincrease and its pH to decrease over time. At periodic intervals duringthe condensation reaction process, the water level is replenished to theinitial volume. The reaction slurry is then diluted with an additional50 g of water and stirred for 30 minutes to further facilitatedispersion of the AlP particles in the reaction slurry. The slurry isthen filtered, washed with a volume of water approximately six times thevolume of the precipitate, and filtered again. This filter-wash-filtercycle can be repeated until the desired purity level is achieved.Usually one to three cycles is sufficient to remove unreacted startingmaterial and unwanted reaction by-products.

As noted above in Example 4, it has been discovered that by allowing thevolume to vary as described during the reaction, the resulting change insystem concentration and pH causes sequential precipitation of AlP“oligomers” in solution onto AlP particles already formed andagglomerated. This sequential precipitation of AlP oligomers ontoalready-formed and agglomerated AlP particles operates to seal thesurface porosity of the pre-existing AlP aggregates and particles, e.g.,causing in-situ particle layering, which thereby reduces the surfaceporosity of such AP aggregate and reduces such related properties as oilabsorption. In an example embodiment, the AP oligomers are AAlP and theAlP particles already formed are AAlP. Additionally, as described above,it is to be understood that the method disclosed herein can be used toproduce crystalline AlP, or combinations of AAlP and crystalline AlP.

Example No. 6 Formation of the Bioactive-AlP Complex (PhysicalIncorporation)

The AlP made as a binary condensation product, e.g., as set forth inExample Nos. 1 to 5, was constituted as a 34 percent by weight slurry,and was mixed with appropriate concentration silver nitrate solution.The later solution was made so that a 1.0% percent and a 10% percentsilver-to-AlP slurry solution was prepared. The combined slurry wasmixed for approximately 5 minutes and then atomized in a spray drierunder nitrogen, and dried at temperatures ranging from about 180° C.inlet to about 79° C. outlet. The solid powder was collected andanalyzed. The resulting powder was a bioactive-AlP complex where thebioactive material was physically incorporated, enmeshed, encapsulated,or intertwined in the AlP polymer.

Alternatively, the AlP made as a binary condensation product, e.g., asset forth in Example Nos. 1 to 5, was constituted as a 34 percent byweight slurry, and was mixed with appropriate concentration silvernitrate solution. After stirring the combined slurry was filtered andwashed once with hot water at a temperature of 40 to 60° C. The filtratewas dried at approximately 110° C. for approximately 12 hours, dividedinto portions, and each heat treated for approximately 24 hours atapproximately 250° C. Yields were the same regardless of heat treatmenttemperature, and the resulting powder was a bioactive-AlP complex wherethe bioactive material was physically incorporated, enmeshed,encapsulated, or intertwined in the AlP polymer.

Example No. 7 Formation of the Bioactive-AlP Complex (Chemical Bonding)

AlPs were prepared by the binary condensation routes described above inExample Nos. 1 to 5, except that a silver nitrate solution ofappropriate concentration was combined at the same time as thephosphoric acid and aluminum hydroxide where brought together. Theresulting suspension comprised the bioactive-AlP complex condensate insolution, wherein the bioactive material, in the form of silver ion, waschemically bonded with the AlP polymer, e.g., incorporated into the AlPpolymer backbone. The suspension was filtered in the manner describedabove, to isolate the bioactive-AlP complex particles. The particleswere washed and dried at the temperatures described in the above-notedExamples to provide the desired engineered physical properties orcharacteristics, e.g., porosity.

In these example processes, a chemical reaction results in the formationof amorphous aluminum orthophosphate or of aluminum orthophosphates(Al₂(HPO₄)₃ or Al(H₂PO₄)₃. The reaction, is carried out through themixture of the two ingredients (when forming the AlP separately), orthrough the mixture of the three ingredients (when directly forming thebioactive-AlP complex). The reagents are dosed in a reactor equippedwith a stirring device, and allowed to react for a short period of time,e.g., less than about 10 minutes.

Precipitation Methods of Making

The AlP is a phosphate complex prepared by dissolving a suitable salt,such as aluminum hydroxide, magnesium hydroxide, calcium hydroxide,aluminum sulfate and the like in phosphoric acid in molar amounts toachieve complete dissolution of the salt. The phosphate complex isprecipitated from the acid solution by neutralizing with an alkalinesolution or base such as sodium hydroxide, potassium hydroxide, ammoniumhydroxide, sodium aluminate, potassium aluminate and the like. Thecomposition of the resulting precipitated solid depends on the ratio ofthe metal to the phosphate anion. The properties of the precipitatedcomplex, i.e., AlP, depend on the processing parameters employed duringthe dissolution of the salt in the acid and on the conditions of theprecipitation/neutralization, including choice of neutralizing agent,temperature, order of addition of reactants, rate of addition ofreactants, and the degree and duration of agitation.

AlPs are made as a precipitation product by combining selected startingmaterials including an aluminum source and a phosphorous source underspecific conditions of controlled material delivery, temperature,agitation, and pH. The judicious selection of starting materials andprocess conditions produces AlPs having a material content and chemicalstructure intentionally created with the purpose of producing theabove-noted engineered physical property or characteristic, e.g.,porosity, the provides the desired controlled delivery/release of thebioactive constituent.

Aluminum sources useful for forming AlP by-precipitation includealuminum salts, such as aluminum chloride, aluminum nitrate, aluminumsulfate and the like. Aluminum sources useful for forming AlP alsoinclude aluminate compounds, such as sodium aluminate and the like,aluminum hydroxide, or aluminum in metallic form. Phosphorous sourcesuseful for forming AlP by precipitation include phosphoric acid, andsalts of phosphorus as orthophosphates or as polyphosphates. An alkalinesolution is used to control the pH or neutralize the reaction of themain ingredients. In an example embodiment, the alkaline solution caninclude ammonium hydroxide, sodium hydroxide, sodium carbonate, andcombinations thereof. In an example embodiment, sodium hydroxide is usedas the alkaline solution. Useful aluminum sources, phosphate sources,and alkaline sources include those disclosed in Published US PatentApplications 2006/0045831 and 2008/0038556, which are each incorporatedherein by reference in their entirety.

AlPs can be made through the selective combination of the materialsnoted above. The following selected methods of preparation are providedbelow as examples, and it is to be understood that other methods ofpreparation other than those specifically disclosed may be used. WhileAlPs produced according to the precipitation route as better disclosedbelow comprise amorphous AlPs, it is to be understood that theprecipitation methods of making AlP as disclosed herein can also be usedor adapted to produce crystalline AlP or combinations of amorphous andcrystalline AlP depending on the particular desired antimicrobialchemical composition properties.

Example No. 8 Aluminum Sulfate Method of Making AlP

In an example embodiment, AlP having the above-noted engineeredproperties is prepared by combining aluminum sulfate, phosphoric acidand sodium hydroxide as disclosed in U.S. Pat. No. 7,951,309, which isincorporated herein by reference. The process steps used in this exampleprocess generally include: preparing the main reagents, such as adiluted solution of phosphoric acid, a diluted solution of aluminumsulfate, and a diluted solution of sodium hydroxide or ammoniumhydroxide; simultaneous and controlled adding of the reagents in areactor equipped with a sloshing system to keep the homogeneity of themixture during the process; and controlling, during the addition of thereagents in the reactor, of the temperature and pH (acidity) of themixture and the reaction time.

The main reagents in this example process can be prepared as follows. Asource of phosphorus is fertilizer grade phosphoric acid, from anyorigin, that has been clarified and discolored. For example, acommercial phosphoric acid containing approximately 54% of P₂O₅ may bechemically treated and/or diluted with treated water resulting in aconcentration of approximately 20% P₂O₅. Another reagent useful for thisexample process is commercial aluminum sulfate, which may be obtained byreaction between alumina (hydrate aluminum oxide) and concentratedsulfuric acid (98% H₂SO₄), that is clarified and stored at anapproximate 28% concentration of Al₂O₃. For the reaction to havefavorable kinetics, the aluminum sulfate is diluted with water treatedat approximately 5% of Al₂O₃.

Neutralization of the reaction is carried out with a sodium hydroxidesolution, which may be commercially purchased in differentconcentrations. A concentration of approximately 50% of NaOH may bepurchased and diluted. For example, in a first phase of the reaction,when the initial reagents are being mixed, the sodium hydroxide may beused in the concentration of approximately 20% of NaOH. In a secondphase of the reaction, to fine tune the product acidity, a sodiumhydroxide solution with approximately 5% of NaOH may be used. As analternative neutralizer, ammonium hydroxide or sodium carbonate (sodaash) may be used.

In this example process, a chemical reaction results in the formation ofamorphous aluminum orthophosphate or of aluminum orthophosphates(Al₂(HPO₄)₃ or Al(H₂PO₄)₃. The reaction is carried out through themixture of the three reagents, i.e., phosphoric acid solution, aluminumsulfate solution, and sodium hydroxide solution. The reagents are dosedin a reactor, typically containing a sloshing system, during about a 30minute period. During the addition of the reagents in the reactor, thepH of the mixture is controlled within a 4 to 4.5 range and a reactiontemperature, between 35° C. and 40° C. The reaction is completed afterabout 15 minutes of the reagent mixture. In this period, the pH of themixture may be adjusted to 5, with the addition of more diluted sodiumhydroxide. In this example process, the temperature is preferablymaintained below approximately 40° C. At the end of the reaction, thesuspension formed should contain a P:Al molar ratio of between about0.8:1 to 1.2:1.

After the formation of the AlP, the suspension containing around 6.0% to10.0% of solids, with a maximum approximate temperature of about 45° C.,and density of about 1.15 to 1.25 g/cm³, is processed for separation. Inan example embodiment, the suspension is pumped to a conventional filterpress. In the filter press, the liquid phase (sometimes referred to asthe “liquor”) is separated from the solid phase (sometimes referred toas the “cake”). The wet cake, containing approximately 35% to 45% ofsolids is kept in the filter for washing cycle. The filteredconcentrate, which is basically a concentrated solution of sodiumsulfate, is extracted from the filter and stored for future usage. Whilethe use of a filter press has been disclosed as a separating technique,it is to be understood that other types of separating techniques can beused.

In an example embodiment, washing of the wet cake is performed in thefilter itself and in multiple process steps. In a first washing(“displacement washing”) the largest part of the filtered substancecontaminating the cake is removed. The washing step is performed usingtreated water over the cake flowing at a preselected flow rate. A secondwashing step, also with treated water, may be carried out to furtherreduce, if not eliminate, the contaminants. A third washing step using aslightly alkaline solution may be used to neutralize the cake and tokeep its pH in the 7.0 range. The cake may be blown with compressed airfor a period of time. Preferably, the solids content of the wet productis between about 35% to 45%. While the use of a particular washingtechnique and sequence has been disclosed, it is to be understood thatother types of washing techniques can be used.

The cake dispersion may be processed in such a way that the filter cake,wet and washed, and containing approximately 35% of solids, is extractedfrom the press filter by a conveyor belt and transferred to areactor/disperser. The dispersion of the cake is aided by the additionof a dilute solution of sodium tetrapyrophosphate.

After the dispersion step, the product is then dried, when the AAlP“mud,” with a percentage of solids of between about 30% to 50%, ispumped to the drying unit. In an example embodiment, water removal fromthe material can be carried out with drying equipment, such as a “turbodryer” type through an injection of a hot air stream, at a temperatureof less than about 300° C., preferably temperatures of from about 100°C. to 200° C. as noted above to obtain the desired engineered porosity.While the use of a particular drying technique has been disclosed, it isto be understood that other types of drying techniques can be used.

Example No. 9 Sodium Aluminate Method of Making AlP

In another example process, the AlP is prepared by using sodiumaluminate as an aluminum source as disclosed in U.S. Pat. No. 7,951,309.In one such embodiment, the AAlP is prepared by a reaction betweenphosphoric acid and aluminum hydroxide. The process may further comprisea step of neutralizing that can be carried out by using sodiumaluminate. In certain embodiments, the process for making an AlPcomprises reacting phosphoric acid, aluminum hydroxide and sodiumaluminate. In one embodiment, the process for making an amorphous sodiumaluminum phosphate comprises reacting aluminum phosphate and sodiumaluminate.

In one embodiment, the reaction comprises two steps. In a first step,phosphoric acid reacts with aluminum hydroxide to produce aluminumphosphate at an acidic pH. In one embodiment, AlP is produced as a watersoluble aluminum phosphate. In certain embodiments, the pH of watersoluble AlP is less than about 3.5. In certain embodiments, the pH isabout 3, 2.5, 2, 1.5 or 1. In certain embodiments, AAlP is produced as afine solid-liquid dispersion at a higher pH. In one embodiment, the pHis about 3, 4, 5 or 6.

In a second step, the acidic aqueous aluminum phosphate solution ordispersion from the first chemical step is reacted with sodiumaluminate. In certain embodiments, the sodium aluminate is used as anaqueous solution at a pH greater than about 10. In one embodiment, thepH of the aqueous sodium aluminate solution is about 11, 12 or 13. Inone embodiment, the pH of the aqueous sodium aluminate solution isgreater than about 12. The AAlP is generated as a solid precipitate. Inone embodiment, the solid aluminum-sodium phosphate has a molar ratio ofP:Al of about 0.85, and a molar ratio of Na:Al of about 0.50. In oneembodiment, the solid AAlP has a molar ratio of P:Al of about 1, and amolar ratio of Na:Al of about 0.76. In certain embodiments, themolecules with other formulation ratios can be obtained by the sameprocedure.

In one embodiment, the solid hydrated aluminum hydroxide is added to thephosphoric acid in the first chemical step. In another embodiment, thesolid hydrated aluminum hydroxide is added to the purified liquid sodiumaluminate solution to form a colloidal solution. In another embodiment,the solid hydrated aluminum hydroxide is added directly as solid orsolid-liquid suspension in water in the second reaction step. In certainembodiments, the reaction is carried out in a single step.

Sodium aluminates useful for this example process include those that canbe obtained by methods known to those skilled in the art. For example,the sodium aluminate can be provided in solution form as a standardchemical product resulting from the first step in the Bayer process inthe alumina (Al₂O₃) extraction from Bauxite ore, often called “purifiedsodium pregnant solution”. This liquid aqueous sodium aluminate solutionis saturated at ambient temperature and stabilized with sodiumhydroxide, NaOH. It's typical compositions are: sodium aluminate, 58 to65% mass (25 to 28% mass of Al₂O₃) and sodium hydroxide, 3.5 to 5.5%mass (2.5 to 4% mass of free Na₂O). In certain embodiments, it has amolar ratio of Na:Al of from about 1.10 to 2.20 and low impurities(depending on the Bauxite origin: Fe=40 ppm, Heavy metals=20 ppm, andsmall amount of anions, Cl⁻ and SO₄ ²⁻). In certain embodiments, thesodium aluminate water solution has a molar ratio of Na:Al of about 1.10, 1.15, 1.20, 1.25, 1.30, 1.35, 1.40, 1.45, 1.50, 1.55, 1.60, 1.65,1.70, 1.75, 1.80, 1.85, 1.90, 1.95, 2.0, 2.05, 2.10, 2.15 or 2.2. Thesolution color, in certain embodiments, is amber. In certainembodiments, the viscosity of the solution is approximately 100 cP. Incertain aspects, the sodium aluminate solution is purified by polishingfiltration. In certain embodiments, the sodium aluminate solution isregenerated from solid aluminum hydroxide and sodium hydroxide.

The solid hydrated aluminum hydroxide can be obtained by methods knownto one of skill in the art. In one embodiment, aluminum hydroxide is anindustrial chemical produced by the Bayer process. The solid hydratedaluminum hydroxide can be obtained from the “purified sodium aluminatepregnant solution” by precipitation which is accomplished via coolingthe solution. In one embodiment, the sodium aluminate thus produced hasa low level of impurities and a variable amount of humidity (cationsabout 70 ppm, chlorates about 0.85% mass and sulfates about 0.60% mass(these impurities are determined by the purification level of the“Purified Sodium Aluminate pregnant solution) and the total water,hydration and humidity, about 22.0 to 23.5% mass. In one aspect, bothraw materials are standard primary industrial products, just first andsecond step from the bauxite processing, (commodities) produced in hugeamounts by the bauxite processors.

In one embodiment, the chemical reaction results in the formation ofaluminum sodium phosphate (Al(OH)₇Na₇(PO₄).1.7H₂O). After the formationof aluminum sodium phosphate, the suspension containing around 6% to 10%of solids, with a maximum approximate temperature of 45° C., and densityin a 1.15 to 1.25 g/cm³ range, is pumped to a conventional filter press.

In a preferred embodiment, AlP prepared by the precipitation process isprepared by using sodium aluminate. It has been discovered that thesodium aluminate process provides for an improved degree of control overthe desired characteristics of the AlP that does not otherwise exist inthe aluminum sulfate process.

Example No. 10 Formation of the Bioactive-AlP Complex (PhysicalIncorporation)

The AlP made by the precipitation methods described above in ExampleNos. 8 and 9, was constituted as a 34 percent by weight slurry, and wasmixed with appropriate concentration silver nitrate solution. The latersolution was made so that a 1.0 percent and a 10 percent by weightsilver-to-AlP complex was made and a slurry solution was prepared. Thecombined slurry was mixed for approximately 5 minutes and then atomizedin a spray drier under nitrogen, and dried at temperatures ranging fromabout 180° C. inlet to about 79° C. outlet. The solid powder wascollected and analyzed. The resulting powder was a bioactive-AlP complexwhere the bioactive material was physically incorporated, enmeshed,encapsulated, or intertwined in the AlP polymer.

Alternatively, the AlP made by the precipitation processes disclosedabove was constituted as a 34 percent by weight slurry, and was mixedwith appropriate concentration silver nitrate solution. After stirringthe combined slurry was filtered and washed once with hot water at atemperature of 40 to 60° C. The filtrate was dried at approximately 110°C. for approximately 12 hours, divided into portions, and each heattreated for approximately 24 hours at approximately 250° C. Yields werethe same regardless of heat treatment temperature, and the resultingpowder was a bioactive-AlP complex where the bioactive material wasphysically incorporated, enmeshed, encapsulated, or intertwined in theAlP polymer.

Example No. 11 Formation of the Bioactive-ALP Complex (Chemical Bonding)

An AlP was prepared similar to the precipitation process described abovein Example Nos. 8 and 9, except that a silver nitrate solution ofappropriate concentration was combined with the acidic aluminumphosphate solution (P:Al ratio of 3:1) and then neutralized with anappropriate amount of sodium aluminate. The resulting dispersioncomprised the bioactive-AlP complex, wherein the bioactive material, inthe form of silver ion, was chemically bonded with, e.g., incorporatedinto the polymer backbone of, the AlP polymer. The dispersion wasfiltered to isolate the bioactive-AALP complex particles. The particleswere washed and dried at the temperatures described above to provide thedesired engineered porosity.

Sol Gel Method of Making

AlP prepared by a sol-gel process involves the creation of inorganicmolecular networks from molecular or ionic precursors through theformation of a colloidal suspension (sol) and the gelation of such solto form a solid network in a continuous liquid phase (gel). Theprecursors for synthesizing these colloids typically comprise a metal ormetalloid element surrounded by various reactive groups. Stated anotherway, in the sol gel process, simple molecular or ionic precursors areconverted into nano-sized particles to form a colloidal suspension(sol). The colloidal nano-particles are then linked with one another ina three-dimensional liquid filled solid network (gel). Thistransformation to a gel can be initiated in a number of ways, but themost convenient approach is to change the pH of the reaction solution.

The method used to remove the liquid from the solid will affect the solgel's properties. For example, supercritical drying will maintain thethree-dimensional structure in the dried solid, whereas slow drying in afluid evaporation process collapses the network structure creating ahigh density material.

Advantages to preparing the AlP via a sol gel synthesis process includeprocess versatility and simplicity resulting in the possibility toobtain highly pure and/or tailored materials, uniform particle sizedistribution, substantially spherical-shaped aggregate particles,nano-sized particles, and custom engineered compositions. While AlP asdisclosed herein comprises substantially spherical aggregate particles,it is understood that some small amount of nonspherical particles mayunintentionally be produced and may be present in the resultingantimicrobial chemical compositions.

As used herein, the term “gel” is understood to be a three-dimensionalcage structure formed of linked large molecular mass polymers oraggregates in which liquid is trapped. The network of the structuretypically consists of weak and/or reversible bonds between the coreparticles. The term “sol” as used herein is understood to be a colloidaldispersion of solids in a liquid. The solids comprise aluminum phosphatehaving nanometer scale average particle sizes. The gel comprises analuminum phosphate sol as a dispersed phase in a semi-rigid massenclosing all of the liquid. Post treatment of product produced by thesol gel process by filtration, washing, drying, and combinations thereofleads to aggregation of the colloidal solids in a controlled fashion toform a larger solid complex.

Generally, the sol gel process includes the following process steps: (1)nucleation or polymerization or condensation of the molecular precursorsto form primary particles, e.g., nanometer in scale, to form the sol(colloidal dispersion or suspension); (2) growth of the particles orgelation; (3) linkage of the particles to form chains and the extensionof such chains throughout the liquid medium to form a thickened gel; and(4) treating the sol gel material to remove the liquid to give a desiredsolid end-product.

In an example embodiment, the precursor solution is prepared bycombining a suitable aluminum source, with a phosphorous source.Suitable aluminum sources can be selected from the group of aluminumsalts such as aluminum chloride, aluminum nitrate, aluminum sulfate andthe like. A preferred aluminum source is aluminum nitrate. Phosphoroussources useful for forming AAlP by sol gel process include phosphoricacid, and salts of phosphorus as orthophosphates or as polyphosphates. Asource of phosphorus is fertilizer grade phosphoric acid, from anyorigin, that has been clarified and discolored.

The primary ingredients of the precursor solution are combined togetherin an aqueous environment with a gelling agent to produce a colloidaldispersion of solid aluminum phosphate particles in solution. In anexample embodiment, the precursor solution is formed by combiningaluminum nitrate with phosphoric acid (85% by weight) in the presence ofwater. Water can be present in one or more of the aluminum nitrate, thephosphoric acid, or as added water independent of either ingredient.

After the precursor ingredients are combined, the resulting system isstirred and a suitable alkaline ingredient is added to the stirredsolution. Alkaline ingredients useful for this purpose include thoseconventionally used to change the pH of the system, e.g., increase thepH of the acidic system, and in an example embodiment is ammoniumhydroxide. The presence of the ammonium hydroxide increases the pH anddrives the process of nucleation and condensation forming a colloidaldispersion or sol. Depending on the concentration of nucleating agent,this step can be intermediate or final. Further addition of nucleatingagent causes the primary aluminum phosphate particles to link togetherforming a gel, e.g., results in gelation, and further results in thecolloidal particles being linked into the gel structure to form a solgel.

In an example embodiment, it may be desired to control the sol gelprocess to isolate the colloidal dispersion before gelation. This can bedone by controlling the reaction conditions so that only colloidaldispersion occurs (i.e., formation of a sol) and not full gelation.Controlling the process in this manner may provide certain manufacturingadvantages and/or provide certain advantages relating to handling of theend-product. The colloidal dispersion from this process can be filteredto recover the solids, and then thermally treated and/or washed asdescribed below.

In an example embodiment, the phosphoric acid, aluminum nitrate, and/orammonium hydroxide can be heated prior to being combined with oneanother, or can be heated after combination, e.g., during stirring.Additionally, the amount of water present and/or the rate of addition ofthe ammonium hydroxide, can be adjusted to produce a desired reactionproduct having a desired yield of AAlP.

In an example embodiment that amount of ammonium hydroxide, NH₄OH, thatis added to the acid solution is sufficient to neutralize the acidsystem to initiate formation of colloidal aluminum phosphate particles,and for gelation exceeds the stoichiometric amount to form ammoniumnitrate, NH₄NO₃. The range can be from the stoichiometric amount ofNH₄OH needed to form the NH₄NO₃ (1.0 stoichiometry) to about 3.0stoichiometry, preferably between about 1.1 and 2.0, and more preferablybetween about 1.2 and 1.5.

The order of addition (i.e., base solution to acid precursor solution orvice versa) has been found to control the rate and extent of gelation.When base is added to stirred precursor solution in stoichiometricconcentration ranges stated above (1.0 to 3.0) virtually instantaneousgelation occurs. It has been discovered that reversing the order ofaddition, i.e., adding the precursor solution to the base solution,provides control over the extent of growth from colloidal dispersion tofull gelation. As discussed below, it has also been discovered thatparticle morphology can be controlled by the method of addition.

It has been found that concentrations of ammonia in excess of the 1.1stoichiometric ratio are useful to minimize unreacted aluminum in theresulting complex. For the end-use application as an inhibitive pigment,it is desirable that the phosphate release rate from the complex whencontacted with water be in the 200 to 400 ppm range. Testing hasdetermined that phosphate anion elution is in the target range when theammonia level in the reaction is around 1.2 to 3 stoichiometric ratioand after the solid has been thoroughly washed and/or thermally treatedto remove the soluble by-products as described below.

In an example process, the sol gel is next subjected to post gelationtreatment which may comprise heating, washing, and/or sizing. In anexample embodiment, the sol gel powder formed is isolated by collapsingthe dispersion or gel by driving off the liquid constituent. Varioustypes of gels can be formed from the sol gel such as; xerogels that aresolids formed by unhindered drying of the sol gel so as to yield highporosity and surface area (150-1,000 m²/g) in solid form, aerogels thatare solids formed by supercritical drying (e.g., freeze drying),hydrogels that are water insoluble colloidal polymer particles dispersedin water, and organogels that are amorphous, non-glassy solidscomprising a liquid organic phase trapped in the solid matrix.

The sol gel consists of solid AlPO₄ connected through various pHdependent (amino, water, phosphate) linkages to form a solid dispersedphase as a mass enveloping all the liquid, the latter consisting ofwater and dissolved salts. Heating the gel, to a temperature above about100° C., evaporates the water and any ammonia and collapses the mass toa solid consisting of aluminum phosphate, AlPO₄, and ammonium nitrate,NH₄NO₃. Heating the gel or the collapsed gel solid, to a temperatureabove about 215° C., thermally decomposes the ammonium nitrate, NH₄NO₃,thereby eliminating it from the powder product. Heating to temperaturesabove about 215° C. leads to a decrease in pH, indicating that residualamino groups remaining after thermal decomposition of the ammoniumnitrate, NH₄NO₃, most likely as substituent's on the PO group, are alsothermally decomposed and replaced by hydrogen atoms thereby making thecomplex acidic. The solid product resulting from this treatment has beenshown by analysis to be pure AAlP having a phosphate release rate ofaround 240 ppm and surface area greater than 125 m²/gram.

Accordingly, the post gelation heat treatment can comprise a single stepof heating the sol gel to a relatively high temperature above about 250°C. for a period of time sufficient to achieve water evaporation,collapsing of the mass, and thermally decomposing the ammonium nitrate,NH₄NO₃. In an example embodiment, this can be done at about 250° C. forapproximately 12 to 72 hours. The resulting product from this heattreatment is substantially aluminum phosphate, i.e., there is verylittle if any ammonium phosphate or ammonium nitrate.

Alternatively, the post gelation heat treatment can comprise a singlestep of heating the sol gel at a lower temperature of about above about100 to 150° C. for a period of time sufficient to achieve waterevaporation. In an example embodiment, this can be done at about 110° C.for approximately 1 to 24 hours. The resulting product from this heatingor drying treatment is AAlP and ammonium phosphate and ammonium nitrate.

This drying step can be followed by a heat treatment step at atemperature of between about 215 to 300° C. In a preferred embodiment,the drying step is at about 110° C. for about 24 hours, and the heattreatment is about 250° C. for up to 1 to 3 days (16 to 72 hours). Theresulting AAlP has a moisture content of from about 5 to 20 percent byweight and the desired engineered porosity. The pH of the heat treatedmaterial can be adjusted by re-dispersing the complex and adjusting thepH with ammonium hydroxide solution. The resulting complex is then driedat 100 to 110° C. to remove water and ammonia.

If desired, before drying or heat treatment, the sol gel material can befiltered to separate the solid particles from solution, and theseparated solid, e.g., in the form of a cake, can be subjected to one ormore wash cycles. The wash cycles use water and operate to rid the solidaluminum phosphate particles of any unwanted solubles, e.g., ammoniumcompounds such as ammonium nitrate, and ammonium phosphate that havebeen formed as a reaction by-product. The washed sample can then bedried and/or heat treated in the manner disclosed above to furtherevaporate water and/or thermally decompose any residual ammonium nitrateand ammonium phosphate in the washed aluminum phosphate, and densify thealuminum phosphate particles.

If desired, the sol material can be dried at about 100° C. to evaporatewater and collapse the mass, and the collapsed powder can be washed withwater to remove ammonium nitrate, NH₄NO₃, to thereby recover instead ofthermally decompose the by-product. The washed and dried mass can beheat treated above about 215° C. to thermally decompose any residualammonium nitrate, NH₄NO₃, thereby providing substantially pure AAlP.

The basic chemistry of the sol gel process for forming only the AAlP ispresented below as follows:

-   -   1. Precursor solution—Combination of all ingredients

Al(NO₃)₃.9H₂O+H₃PO₄+H₂O

-   -   2. Gelling Agent

3NH₄OH+H₂O

-   -   3. Sol-gel reaction

AlPO₄+(NH₄)₃PO₄+H₂O→AlPO₄+NH₄OH

Reaction to form AAlP sol gel: as NH₄OH (28% NH₃ in water) is added, itneutralizes the acid system and drives formation of insoluble AlPO₄,that takes Al⁺³ out of the reaction and allows more NH₄ ⁺¹ to combinewith NO₃ ⁻¹ to form soluble NH₄NO₃. Depending on the concentration andrate of addition of the NH₄OH colloidal particles of AlPO₄ will form.Adding more NH₃ to the reaction allows the AlPO₄ colloidal particles toaggregate and to eventually form bonds between the particles to form thegel structure.

The amount of NH₃ added must exceed the stoichiometric amount requiredto form NH₄NO₃ in order to have sufficient NH₃ to control pH andfacilitate gel bridging. Depending on the amount of NH₃ added, the rateof addition, and the concentration, the gel will consist of a mass ofAlPO₄ solid particles linked forming a cage, three-dimensional structureencapsulating ammonium nitrate, NH₄NO₃, dissolved in water. Ammoniumphosphate may also be present as an intermediate, and extending reactionconditions (i.e., by further heating) will lead to full reaction withthe aluminum in the system to condense to aluminum phosphate.

4. Filtration and washing—Optional to supplement or replace thermalpurification to remove soluble ammonium salts.

5. Dehydration and drying—Drying at above at least 100° C. to evaporatewater and collapse the sol gel structure to form a densified solid.

AlPO₄+NH₄NO₃

-   -   6. Thermal purification—Thermal treatment at 215 to 250° C. to        thermally decompose ammonium nitrate.

AlPO₄ (amorphous aluminum phosphate)

If desired, the order of ingredient addition can be changed from thatdisclosed above. For example, the acid solution may be added to asolution of the ammonium hydroxide in order to control the viscosity ofthe reaction system and/or impact the surface area of the colloidalsolids. Such flexibility in the order of ingredient addition may beadvantageous, e.g., for the scale-up of manufacturing where it may bedesirable to avoid gelation in favor of the formation of a suspension ofcolloidal primary particles. The resulting composition after washing,drying and/or thermal treatment is essentially chemically the sameregardless of the order of addition. However product morphology isaffected by these processing parameters. Adding acid to base results inhigher surface area and greater porosity. The sol gel process disclosedherein produces an aluminum phosphate composition consisting essentiallyof AAlP.

Base-to-acid sequencing causes rapid pH change and the rapid formationof sol particles followed by rapid gelation to form interlinkedparticles in the gel matrix. This reduces molecular mobility andprevents any further particle growth or morphological change. When acidis added to base, the pH change is slower and localized colloidalaluminum phosphate particles form. No gelation occurs so the systemmobility allows for continued competing side reactions (increasedsolublization of ammonium nitrate and ammonium phosphate) allowingintermediate species to survive. When dehydration and thermaldecomposition occur, small particles of aluminum phosphate exist in thepresence of departing water and decomposition products (of ammoniumnitrate), leading to more porosity in small aggregated aluminumphosphate particles.

The basic chemistry of the sol gel process for forming only thebioactive-AAlP complex (which involves adding the bioactive material,e.g., in the form of silver nitrate, to the aluminum nitrate and aqueousphosphoric acid) is presented below as follows:

-   -   1. Precursor solution—Combination of all ingredients

Al(NO₃)₃.9H₂O+H₃PO₄+H₂O+AgNO₃

-   -   2. Gelling Agent        3NH₄OH+H₂O    -   3. Sol-gel reaction

AgAlPO₄+(NH₄)₃NO₃+H₂O+NH₃

-   -   4. Filtration and washing—Optional to supplement or replace        thermal purification to remove soluble ammonium salts.    -   5. Dehydration and drying—Drying at above at least 100° C. to        evaporate water and collapse the sol gel structure to form a        densified solid.

AgAlPO₄+NH₄NO₃

-   -   6. Thermal purification—Thermal treatment at 215 to 250° C. to        thermally decompose ammonium nitrate.

AgAlPO₄ (amorphous silver aluminum phosphate)

Example No. 12—Formation of the Bioactive-AlP Complex (PhysicalIncorporation)

The AAlP made by the sol gel process as described above, was constitutedas a 34 percent by weight slurry, and was mixed with appropriateconcentration silver nitrate solution. The later solution was made sothat a 1.0 percent and a 10 percent silver-to-AgAlP complex wereprepared. The combined slurry was mixed for approximately 5 minutes andthen atomized in a spray drier under nitrogen, and dried at temperaturesranging from about 180° C. inlet to about 79° C. outlet. The solidpowder was collected and analyzed. The resulting powder was abioactive-AlP complex where the bioactive material was physicallyincorporated, enmeshed, encapsulated, or intertwined in the AlP polymer.

Alternatively, the AAlP made by the sol gel process was constituted as a34 percent by weight slurry, and was mixed with appropriateconcentration silver nitrate solution. After stirring the combinedslurry was filtered and washed once with hot water at a temperature of40 to 60° C. The filtrate was dried at approximately 110° C. forapproximately 12 hours, divided into portions, and each heat treated forapproximately 24 hours at approximately 250° C. Yields were the sameregardless of heat treatment temperature, and the resulting powder was abioactive-AlP complex where the bioactive material was physicallyincorporated, enmeshed, encapsulated, or intertwined in the AlP polymer.

Example No. 13—Formation of the Bioactive-AAlP Complex (ChemicalBonding)

An AAlP was prepared similar to the sol gel process described above,except that a silver nitrate solution of appropriate concentration wascombined at the same time as the aluminum nitrate and aqueous phosphoricacid. The resulting gel comprised the bioactive-AlP complex, wherein thebioactive material, in the form of silver ion, was chemically bondedwith the AlP polymer. The dispersion was filtered, washed, and dried atthe temperatures described above to provide the desired engineeredporosity.

AlPs/bioactive-AlP complexes formed by the above-noted methods have aP:Al ratio of from about 0.5:1 to 1.5:1. It is desired that theAlPs/bioactive-AlP complexes have a P:Al ratio in this range becausethis provides a suitable range of particle morphology and propertiesthat are compatible with desired formulation chemistries.

If desired, the bioactive-AlP complex as described herein can beinitially made in the form of a concentrate, wherein an amount of thebioactive material is initially combined with a first amount of the AlP(in the case where the bioactive material is physically incorporatedwith the AlP polymer) or a first amount of the precursor materials usedto form the AlP (in the case where the bioactive material is chemicallybonded with the AlP polymer). This initially stage results in theformation of a bioactive-AlP complex condensate, i.e., having a highconcentration of the bioactive material present. This complex condensatecan then be used as feedstock to formulate a number of differentformulations to meet different end-use applications. In an exampleembodiment, the complex condensate may be combined with further AlP toprovide a bioactive-AlP complex having a relatively lower bioactivematerial content that is well suited for a certain end-use application.The ability to make such a complex condensation thereby adds a desireddegree of flexibility to the process of obtaining differentantimicrobial formulations for meeting different antimicrobial end-useapplications.

AlP and bioactive-AlP complexes made in the manner described herein areprovided in solid form as a white powder having a desired particle sizeor size distribution. The particle size will depend on such factors suchas the binding polymer, and the particular end-use application. In anexample embodiment, the AlP may have a particle size distribution of D50from about 0.5 to 8 microns. In an example embodiment, it is desiredthat the AlP have a P:Al ratio of from about 0.9 to 1, and have aparticle size distribution of D50 of about 1 micron and D90 less thanabout 4 microns. For use in an antimicrobial chemical composition it isdesired that the AlP have a particle size of less than about 20 microns,and preferably in the range of from about 0.5 to 10 microns, and morepreferably in the range of from about 1.0 to 8.0 microns. Particle sizesof less than about 0.5 microns may interfere with the processing ofcertain chemical formulations and adversely affect film properties byincreasing binder resin absorption.

AlP and bioactive-AlP complexes prepared in the manner described abovemay not be subjected to high-temperature drying or other thermaltreatment for the purpose of retaining an amorphous structure andavoiding conversion to a crystalline structure. It has been discoveredthat AlPs formed in this manner retain the desired amorphous structure,even after low temperature drying. AlPs formed as disclosed herein havea structure comprising an engineered porosity that enables it to serveas a carrier for the bioactive material to provide the desiredcontrolled delivery/release of the bioactive constituent for use in anantimicrobial chemical composition.

AAlPs as produced herein display a markedly increased water adsorptionpotential or degree of rehydration, when compared to crystalline AlP,that permits such AAlPs, once dehydrated by drying, to be rehydrated tocontain up to about 25 percent by weight water. This feature isespecially useful when the AlP is used in end-use applications callingfor some degree of protection against corrosion, and wherein the AlP ispresent in a nonwater-borne binding polymer. In such application, theAlP acts, in addition to being a carrier for the bioactive material andbeing an corrosion inhibiting pigment, as a moisture scavenger to bothslow water intrusion into the cured film and restrict water diffusionthrough the cured film.

Additionally, the rehydration feature of AlPs disclosed herein can bebeneficial when placed in low humidity end-use applications. In suchapplications, AlPs can be used having a high or saturated moisturecontent that can operate to drive the bioactive constituent, e.g., havea built-in transport mechanism, to a surface of the cured antimicrobialchemical composition or composite to promote the presence of suchbioactive constituent at the surface in the absence of surroundingmoisture. Engineered in this manner, antimicrobial chemical compositionscomprising such AlP can function to provide a desired level of bioactiveconstituent at the surface in low humidity/moisture applications.

Antimicrobial chemical compositions described herein are prepared bycombining a selected binding polymer with the AlP and the bioactivematerial in the manner and in the amounts described above. The resultingbioactive-AlP complex can be provided for composition formulation in theform of a dried powder or can be provided in the form of a slurry orliquid suspension depending on the formulation conditions orpreferences.

Antimicrobial chemical compositions described herein, comprising thebioactive-AlP complex, comprise from about 5 to 1000 ppm, preferably 10to 900 ppm, and 15 to 800 ppm of the bioactive material based on thetotal weight of the chemical composition. Such antimicrobial chemicalcompositions may comprise other materials, agents, and/or additives (inaddition to the bioactive-AlP complex and the binding polymer), such aspigments, fillers, rheological agents, flow stabilizers, light-controlstabilizers, and the like. For example, antimicrobial chemicalcompositions comprising a silver bioactive material may comprise anadditive designed to inhibit the photo reduction of the silver, tothereby preserve the active state of the silver, contained within thecomposition, dried film and/or composite formed therefrom, to helpensure its effective service life.

Antimicrobial chemical composition disclosed herein may be provided inthe form of a coating composition for applying to a desired substratesurface to provide a desired level of antimicrobial resistance. Suchantimicrobial coating compositions can be formulated for use as aprimer, a mid coat, or a top coat. Additionally such antimicrobialcoating compositions may be used with or without a primer, as a mid or atop coat. Further, antimicrobial chemical compositions as disclosedherein may be formulated as a clear coating for placement over anexisting substrate surface or underlying coating that may or may not becolored, thereby facilitating use of such clear coating over a varietyof substrates or underlying coating surface to provide antimicrobialresistance without the need for special pigmenting to match existingsubstrate colors or the like.

Bioactive-AlP complexes as described herein provide bioactive componentsin a manner that ensures surface antimicrobial efficacy while permittingease of formulation to meet a variety of end-use applications. Thebioactive-AlP complex provides for uniform distribution of the bioactiveingredient, e.g., silver ion, throughout the chemical composition, driedfilm, composite, or formulated article. The bioactive-AlP complexprovides the formulated bulk matrix with properties engineered toaccommodate moisture induced transport: absorption, adsorption,desorption, diffusion of water and dissolved species in bulk. Thebioactive-AlP complex is specifically engineered to release a bioactiveconstituent, e.g., silver ion, based on the concentration of thebioactive material incorporated and by the hydrophilicity and morphologyof the complex (surface area and porosity). The bioactive-AlP complex asdescribed herein can be introduced into formulated products such aspigments, or as an additive through bonding the phosphate functionalityto certain functional groups of the binder matrix of the bulk compositeor film. Additionally, the bioactive-AlP complexes in thermally stableform can be incorporated into powder coating formulations to render suchsurfaces antimicrobial.

In one example embodiment, antimicrobial chemical compositions asdescribed herein can be formulated into a film in which the bulk of thearticle serves as a reservoir or depot for the bioactive material or itsconstituent, e.g., silver ion. Such formulation can be engineered tooptimize the following aspects of the antimicrobial mechanism: waterdiffusion into the film, water absorption and adsorption into thebioactive-AlP complex, salt dissolution within the complex, iontransport out of the complex, and bioactive material or its constituenttransport through the matrix to the surface to be protected.

Alternatively, the antimicrobial chemical compositions as describedherein can be formulated into an enriched thin film (e.g., having a filmthickness of less than about 25 μ, and preferably less than about 10 μ)engineered for physical durability balanced with waterdiffusion/bioactive material or its constituent transport properties toimpart antimicrobial properties to a surface without incorporating theantimicrobial into the bulk of the article, e.g., where suchincorporation may not be practical from a cost standpoint, or where theoperative control mechanism may not be possible, e.g., a waterimpermeable plastic.

As described above, the combined AlP and bioactive material is providedin the form of a bioactive-AlP complex, where the bioactive material iseither chemically bonded with, e.g., provided in the backbone of the AlPpolymer, or is physically incorporated, enmeshed, encapsulated, orintertwined with the AlP polymer, depending on the particular methodused to make the complex. Additionally, the bioactive material or itsconstituent may be present in the AlP polymer both chemically andphysically. For example, when the bioactive-AlP complex is formed bycombining the desired bioactive material at the time of forming the AlP,thereby facilitating chemical bonding between the bioactive material orits constituent with the AlP, a stoichiometric excess of the additionalbioactive material may result in it being physically incorporated intothe AlP molecule, in which case the resulting bioactive-AlP complexwould include the bioactive material or its constituent present in bothchemically-bonded and physically-incorporated form.

As demonstrated above, embodiments of the invention provide a novelantimicrobial chemical compositions, novel bioactive-AlP complexes, andnovel methods for making the same. While each has been described withrespect to a limited number of embodiments, the specific features of oneembodiment should not be attributed to other embodiments of theinvention. No single embodiment is representative of all aspects of theinvention. In some embodiments, the compositions or methods may includenumerous compounds or steps not mentioned herein.

For example, if desired, antimicrobial chemical compositions can beprepared to additionally include one or more bioactive materialsseparately or in combination other than those specifically describedthat are known to have bioactive value. Any such additional bioactivematerial may or may not be incorporated with the bioactive-AlP complex,e.g., can exist as a separate dispersion with the binding polymer, andcan operate to increase or complement or provide a synergisticantimicrobial effect of the chemical composition.

Additionally, while antimicrobial chemical compositions as presented inthe examples provided herein have been described as comprising AlP inamorphous form, it is to be understood that antimicrobial chemicalcompositions as described herein can additionally comprise AlP in itsknown crystalline forms, and can comprise AlP in a combination ofamorphous and crystalline forms.

In other embodiments, the compositions or methods do not include, or aresubstantially free of, any compounds or steps not enumerated herein.Variations and modifications from the described embodiments exist. Themethod of making the chemical compositions and/or AlP is described ascomprising a number of acts or steps. These steps or acts may bepracticed in any sequence or order unless otherwise indicated. Finally,any number disclosed herein should be construed to mean approximate,regardless of whether the word “about” or “approximately” is used indescribing the number. The appended claims intend to cover all thosemodifications and variations as falling within the scope of theinvention.

1-16. (canceled)
 17. A method for making a bioactive-aluminum phosphatecomplex comprising the steps of: forming an aluminum phosphate bycombining an aluminum source, with a phosphate source in an aqueoussolution at suitable pH to form a dispersion of aluminum phosphateparticles; and adding a bioactive material in a form to provide metalions, wherein the step of adding is performed such that the metal ionsare combined with the aluminum phosphate particles to form thebioactive-aluminum phosphate complex; wherein the complex has a porosityengineered to provide a controlled release of the metal ions therefromof from 10 to 1,000 ppm upon contact of the complex with moisture. 18.The method as recited in claim 17 wherein the complex has a porositycharacterized by a BET surface area from about 2 to 250 m²/g.
 19. Themethod as recited in claim 17 wherein the metal ions are chemicallybonded to the aluminum phosphate particles.
 20. The method as recited inclaim 17 wherein the metal ions are selected from the group consistingof silver, copper, zinc, calcium, and combinations thereof.
 21. Themethod as recited in claim 20 wherein the metal ions are silver ions.22. The method as recited in claim 17 wherein the step of formingcomprises combining aluminum hydroxide with phosphoric acid to form thedispersion of aluminum phosphate particles.
 23. The method as recited inclaim 17 wherein the complex has a porosity characterized by at leastone of: a total intrusion volume of 0.5 to 2 mL/g; an average porediameter of from about 0.02 to 0.6 μm; or a BET surface area from about2 to 250 m²/g.
 24. The method as recited in claim 17 wherein thealuminum phosphate particles comprise amorphous aluminum phosphate. 25.A method for making an antimicrobial chemical complex comprising abioactive constituent in the form of metal ions, the method comprisingthe steps of: forming an aluminum phosphate by combining aluminumhydroxide with phosphoric acid in an aqueous solution at suitable pH toform a dispersion of aluminum phosphate particles, the aluminumphosphate comprising amorphous aluminum phosphate; and adding abioactive material during or after the step of forming, wherein thebioactive material comprises metal ions that combine with the aluminumphosphate particles to form the antimicrobial chemical complex capableof providing a controlled release of the metal ions upon exposure tomoisture.
 26. The method as recited in claim 25 wherein theantimicrobial chemical complex has a porosity characterized by at leastone of: a total intrusion volume of 0.5 to 2 mL/g; an average porediameter of from about 0.02 to 0.6 μm; or a BET surface area from about2 to 250 m²/g.
 27. The method as recited in claim 25 wherein, during thestep of adding, the metal ions chemically bond to the aluminum phosphateparticles.
 28. The method as recited in claim 25 wherein the metal ionsare silver ions, and wherein the controlled delivery of silver ions isfrom about 10 to 1,000 ppm.
 29. The method as recited in claim 25wherein the complex further comprises metal ions selected from the groupconsisting of copper, zinc, calcium, and combinations thereof.
 30. Themethod as recited in claim 25 wherein, during the step of forming, firstforming an acid solution phosphate solution by combining a first amountof the aluminum hydroxide with the phosphoric acid to form an acidicaluminum phosphate solution, and then subsequently combining thesolution with further aluminum hydroxide to form the aluminum phosphateparticles.
 31. The method as recited in claim 30 wherein the step ofadding takes place before the aluminum phosphate solution is combinedwith further aluminum hydroxide.
 32. A method for making anantimicrobial chemical composition comprising adding the antimicrobialchemical complex prepared according to claim 25 to a binding polymer.33. The method as recited in claim 32 wherein the complex as disposed inthe binder comprises amorphous aluminum phosphate.
 34. (canceled) 35.The method as recited in claim 17 wherein the controlled delivery of thebioactive constituent is at least about 30 μg/m².
 36. The method asrecited in claim 17 wherein the amount of the metal ions in the complexis in the range of from about 1 to 10 percent by weight of the totalcomplex.
 37. The method as recited in claim 32 comprising in the rangeof from about 0.1 to 2 weight percent of the metal ions based on thetotal weight of the chemical composition. 38-44. (canceled)